The Makorin lep-2 and the lncRNA lep-5 regulate lin-28 to schedule sexual maturation of the C. elegans nervous system

Most animals develop from juveniles, which cannot reproduce, to sexually mature adults. The most obvious signs of this transition are changes in body shape and size. However, changes also take place in the brain that enable the animals to adapt their behavior to the demands of adulthood. For example, fully fed adult male roundworms will leave a food source to search for mates, whereas juvenile males will continue feeding. The transition to sexual maturity needs to be carefully timed. Too early, and the animal risks compromising key stages of development. Too late, and the animal may be less competitive in the quest for reproductive success. Cues in the environment, such as the presence of food and mates, interact with timing mechanisms in the brain to trigger sexual maturity. But how these mechanisms work – in particular where and how an animal keeps track of its developmental stage – is not well understood. In the roundworm species Caenorhabditis elegans, waves of gene activity, known collectively as the heterochronic pathway, determine patterns of cell growth as animals mature. Through further studies of these worms, Lawson et al. now show that these waves also control the time at which neural circuits mature. In addition, the waves of activity occur inside the nervous system itself, rather than in a tissue that sends signals to the nervous system. Moreover, they occur independently inside many different neurons. Each neuron thus has its own molecular clock for keeping track of development. Several of the genes critical for developmental timekeeping in worms are also found in mammals, including two genes that help to control when puberty starts in humans. If one of these genes – called MKRN3 – does not work correctly, it can lead to a condition that causes individuals to go through puberty several years earlier than normal. Studying the mechanisms identified in roundworms may help us to better understand this disorder. More generally, future work that builds on the results presented by Lawson et al. will help to reveal how environmental cues and gene activity interact to control when we become adults.